Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study.

BACKGROUND: Standard interpretations of the ethical principle of respect for persons have not incorporated the views and values of patients, especially patients from groups underrepresented in research. This limits the ability of research ethics scholarship, guidance, and oversight to support inclusive, patient-centered research. This study aimed to identify the practical approaches that patients in community-based settings value most for conveying respect in genomics research. METHODS: We conducted a 3-round, web-based survey using the modified Delphi technique to identify areas of agreement among English-speaking patients at primary care clinics in Washington State and Idaho who had a personal or family history of cancer. In Round 1, respondents rated the importance of 17 items, identified in prior qualitative work, for feeling respected. In Round 2, respondents re-rated each item after reviewing overall group ratings. In Round 3, respondents ranked a subset of the 8 most highly rated items. We calculated each item's mean and median rankings in Round 3 to identify which approaches were most important for feeling respected in research. RESULTS: Forty-one patients consented to the survey, 21 (51%) completed Round 1, and 18 (86% of Round 1) completed each of Rounds 2 and 3. Two sets of rankings were excluded from analysis as speed of response suggested they had not completed the Round 3 ranking task. Respondents prioritized provision of study information to support decision-making (mean ranking 2.6 out of 8; median ranking 1.5) and interactions with research staff characterized by kindness, patience, and a lack of judgment (mean ranking 2.8; median ranking 2) as the most important approaches for conveying respect. CONCLUSIONS: Informed consent and interpersonal interactions are key ways that research participants experience respect. These can be supported by other approaches to respecting participants, especially when consent and/or direct interactions are infeasible. Future work should continue to engage with patients in community-based settings to identify best practices for research without consent and examine unique perspectives across clinical and demographic groups in different types of research.

Motivations and concerns of patients considering participation in an implementation study of a hereditary cancer risk assessment program in diverse primary care settings.

PURPOSE: Understanding the motivations and concerns of patients from diverse populations regarding participation in implementation research provides the needed evidence about how to design and conduct studies for facilitating access to genetics services. Within a hereditary cancer screening study assessing a multifaceted intervention, we examined primary care patients' motivations and concerns about participation. METHODS: We surveyed and interviewed study participants after they enrolled, surveyed those who did not complete enrollment, and used descriptive qualitative and quantitative methods to identify motivations and concerns regarding participation. RESULTS: Survey respondents' most common motivations included a desire to learn about their future risk (81%), receiving information that may help family (58%), and a desire to advance research (34%). Interviews revealed 3 additional important factors: affordability of testing, convenience of participation, and clinical relationships supporting research decision-making. Survey data of those who declined enrollment showed that the reasons for declining included concerns about privacy (38%), burdens of the research (19%), and their fear of not being able to cope with the genetic information (19%). CONCLUSION: Understanding the facilitating factors and concerns that contribute to decisions about research may reveal ways to improve equity in access to care and research that could lead to greater uptake of genomic medicine across diverse primary care patient populations.

An accessible, relational, inclusive, and actionable (ARIA) model of genetic counseling compared with usual care: Results of a randomized controlled trial.

PURPOSE: Effective approaches to communicate genomic information are needed to ensure equitable care. In a randomized controlled superiority trial, we tested a novel practice model that aims to make genetic counseling inclusive, by making the communication accessible, relational, and actionable (ARIA). METHODS: In total, 696 English- and Spanish-speaking patients aged 18 to 49 years, enriched for individuals from historically underserved backgrounds, were randomized in 1:1 ratio to ARIA or usual care. Primary outcomes were accuracy of recall, communication satisfaction, and perceived understanding. In total, 33 participants completed qualitative interviews. RESULTS: Recall and understanding were high for all participants. ARIA participants scored higher on the relationship scale of communication satisfaction (mean difference = 0.09, 95% CI = <0.01 to 0.17). Moderator analyses of communication satisfaction showed that those with lower health literacy reported less communication difficulty in ARIA and those using medical interpreters reported greater communication ease in ARIA. No significant difference was found on other primary and secondary outcomes. Qualitative data enhanced understanding of how and why ARIA can be effective. CONCLUSION: This study provides evidence that a genetic counseling intervention that focuses on specific communication skills to enhance relationship-building, patient engagement, and comprehension can be effective with all patients and may be especially valuable for patients of lower health literacy and Spanish-speakers who use a medical interpreter.

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

BACKGROUND: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study. METHODS: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool. RESULTS: Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history. CONCLUSIONS: Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool. TRIAL REGISTRATION: This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.

Integrating stakeholder feedback in translational genomics research: an ethnographic analysis of a study protocol's evolution.

PURPOSE: This study describes challenges faced while incorporating sometimes conflicting stakeholder feedback into study design and development of patient-facing materials for a translational genomics study aiming to reduce health disparities among diverse populations. METHODS: We conducted an ethnographic analysis of study documents including summaries of patient advisory committee meetings and interviews, reflective field notes written by study team members, and correspondence with our institutional review board (IRB). Through this analysis, we identified cross-cutting challenges for incorporating stakeholder feedback into development of our recruitment, risk assessment, and informed consent processes and materials. RESULTS: Our analysis revealed three key challenges: (1) balancing precision and simplicity in the design of study materials, (2) providing clinical care within the research context, and (3) emphasizing potential study benefits versus risks and limitations. CONCLUSIONS: While involving patient stakeholders in study design and materials development can increase inclusivity and responsiveness to patient needs, patient feedback may conflict with that of content area experts on the research team and IRBs who are tasked with overseeing the research. Our analysis highlights the need for further empirical research about ethical challenges when incorporating patient feedback into study design, and for dialogue with genomic researchers and IRB representatives about these issues.

Demonstrating 'respect for persons' in clinical research: findings from qualitative interviews with diverse genomics research participants.

The ethical principle of 'respect for persons' in clinical research has traditionally focused on protecting individuals' autonomy rights, but respect for participants also includes broader, although less well understood, ethical obligations to regard individuals' rights, needs, interests and feelings. However, there is little empirical evidence about how to effectively convey respect to potential and current participants. To fill this gap, we conducted exploratory, qualitative interviews with participants in a clinical genomics implementation study. We interviewed 40 participants in English (n=30) or Spanish (n=10) about their experiences with respect in the study and perceptions of how researchers in a hypothetical observational study could convey respect or a lack thereof. Most interviewees were female (93%), identified as Hispanic/Latino(a) (43%) or non-Hispanic white (38%), reported annual household income under US$60 000 (70%) and did not have a Bachelor's degree (65%); 30% had limited health literacy. We identified four key domains for demonstrating respect: (1) personal study team interactions, with an emphasis on empathy, appreciation and non-judgment; (2) study communication processes, including following up and sharing results with participants; (3) inclusion, particularly ensuring materials are understandable and procedures are accessible; and (4) consent and authorisation, including providing a neutral informed consent and keeping promises regarding privacy protections. While the experience of respect is inherently subjective, these findings highlight four key domains that may meaningfully demonstrate respect to potential and current research participants. Further empirical and normative work is needed to substantiate these domains and evaluate how best to incorporate them into the practice of research.

Reexamining the categorical exclusion of pediatric participants from controlled human infection trials.

Controlled human infection (CHI) models have been developed for numerous pathogens in order to better understand disease processes and accelerate drug and vaccine testing. In the past, some researchers conducted highly controversial CHIs with vulnerable populations, including children. Ethical frameworks for CHIs now recommend vulnerable populations be excluded because they cannot consent to high risk research. In this paper we argue that CHI studies span a wide spectrum of benefit and risk, and that some CHI studies may involve minimal risk. The categorical exclusion of children from CHIs therefore departs from the standard approach to evaluating research risks, as international regulations and ethical guidance for pediatric research generally permit non-beneficial research with low risks. The paradigm in research ethics has also shifted from focusing on protecting vulnerable participants to recognizing that inclusion can be important as a matter of justice, providing new reasons to question this default exclusion of children from CHIs. Recognizing that pediatric CHIs can raise complex ethical issues and are easy to sensationalize in ways that may threaten the public's trust in research and sponsor institutions, we conclude by describing additional complexities that must be addressed before pediatric CHIs beyond licensed vaccine studies might be ethically acceptable.

The evolving landscape of expanded carrier screening: challenges and opportunities.

Carrier screening allows individuals to learn their chance of passing on an autosomal or X-linked condition to their offspring. Initially introduced as single-disease, ancestry-based screening, technological advances now allow for the possibility of multi-disease, pan-ethnic carrier screening, which we refer to as "expanded carrier screening." There are numerous potential benefits to expanded carrier screening, including maximizing the opportunity for couples to make autonomous reproductive decisions, and efficiency and marginal additional costs of including more conditions if the test is already being offered. While numerous laboratories currently offer expanded carrier screening services, it is not yet commonly used in clinical practice, and there is a lack of consensus among experts about the service, including whether this should be offered to individuals and couples, whether this should be offered preconception or prenatally, and what conditions to include in screening programs. Challenges for expanded carrier screening programs include a lack of demand from the public, low prioritization by health systems, the potential for pressure to undergo screening, the possibility of disability-based discrimination, needed adaptations to pre- and post-test counseling, technical limitations, and the evolving technological and socio-political landscape.